Chronic stress elicits prolonged activation of α-MSH secretion and subsequent degeneration of melanotroph
Chronic stress elicits prolonged activation of α-MSH secretion and subsequent degeneration of melanotroph
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DOI：
10.1111/j.1471-4159.2009.06057.x
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发表时间：
2009-06-01
影响因子：
4.7
通讯作者：
Kiyama, Hiroshi
中科院分区：
文献类型：
--
作者：
Ogawa, Tokiko;Shishioh-Ikejima, Nobue;Kiyama, Hiroshi
长期的压力会影响各种器官的体内平衡，并诱发与压力相关的疾病。我们使用大鼠模型研究了持续应激条件下脑垂体细胞的变化，在该模型中，大鼠被保持在充满水的笼子中，高度为1.5 cm，长达5天。在垂体激素mRNA中，阿黑皮素原mRNA在该大鼠模型的中叶（IL）中特异性上调。此外，α-黑素细胞刺激激素（α-MSH）（IL中阿黑皮素原的主要产物）的外周血水平升高。α-MSH分泌细胞，黑素营养细胞，在实验的早期阶段显示出显着发达的内质网和高尔基体。随后的持续压力引起显着的扩张内质网，破坏高尔基体结构，和一些黑素营养细胞的退化。此外，IL组下丘脑多巴胺能神经纤维明显减少。多巴胺拮抗剂可引起正常大鼠促黑素细胞类似的形态学变化。这些发现表明，长期的压力抑制下丘脑衍生的多巴胺释放IL，这引起过度分泌的α-MSH从黑素营养细胞。目前的研究还表明，内分泌细胞的长期过度激活可能导致分泌机制的紊乱和最终的退化。
Prolonged stress affects homeostasis in various organs and induces stress-associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus-derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.